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Randomized On-X Anticoagulation Trial (PROACT)

Primary Purpose

Heart Valve Disease

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
On-X valve using reduced anticoagulation
On-X Valve with Standard warfarin Therapy
Sponsored by
On-X Life Technologies, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Heart Valve Disease focused on measuring valve, prosthesis, antithrombotics, randomized

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients requiring isolated aortic valve replacement (AVR), or isolated mitral valve replacement (MVR). AVR patients receiving low dose or antiplatelet only anticoagulation will be divided into groups at low risk and high risk for thromboembolism with all patients being in the low risk group except for patients with the following conditions which place a patient in the high risk group: Chronic atrial fibrillation Left ventricular ejection fraction < 30 % Enlarged left atrium >50mm diameter Spontaneous echo contrasts in the left atrium Vascular pathology Neurological events Hypercoagulability Left or right ventricular aneurysm Lack of platelet response to aspirin or clopidogrel Women receiving estrogen replacement therapy Concomitant cardiac surgery is allowed Adult patients Exclusion Criteria: Right side valve replacement Double (aortic plus mitral) valve replacement Patients with active endocarditis at the time of implant Previous confirmed or suspected thromboembolic event or thrombophlebitis Other terminal illness Patients who are in an emergency state Inability to return for required follow-ups Patients with an On-X valve implanted within the study and subsequently explanted Patients who are known to be pregnant, plan to become pregnant or are lactating Patients with acquired immunodeficiency syndrome or know to be HIV positive Patients who are prison inmates or known drug or alcohol abusers Patients unable to give adequate informed consent.

Sites / Locations

  • Tucson Medical Center
  • Southern Arizona VA Medical Center
  • Loma Linda University
  • Hartford Hospital
  • Christiana Health Care Services
  • Medstar Heart & Vascular Institute
  • Shands Hospital - University of Florida
  • Cardiac Surgical Associates
  • South Florida Heart & Lung
  • Florida Hospital
  • Emory University
  • St. Francis Heart Center
  • Cotton-O'Neil Clinical Research Center
  • University of Kentucky
  • Maine Medical Center
  • Brigham & Women's Hospital
  • Beth Israel Deaconess Medical Center
  • St. Joseph Mercy Hospital
  • Mid America Heart institute
  • Barnes Jewish Hospital - Washington University
  • New Mexico Heart Institute
  • St. Luke's Roosevelt
  • Montefiore Medical Center
  • WakeMed
  • Duke University Medical Center
  • Novant Health
  • University Hospital - Cleveland
  • Cleveland Clinic
  • Ohio State University Medical Center
  • University of Oklahoma/VA Oklahoma City
  • Providence Heart & Vascular Institute
  • University of Pittsburgh Medical Center
  • Baylor Research Institute
  • University of Texas Southwestern Medical Center
  • University of Texas Health Science Center at Houston
  • Texas Heart Institute
  • Texas Cardiac Center
  • Baylor Scott & White - Plano
  • Mary Washington Hospital
  • Sentara Norfolk General Hospital
  • Swedish Medical Center
  • MultiCare Health System
  • West Virginia University
  • St. Luke's Aurora Health Care
  • University of Alberta
  • University of British Columbia
  • London Health Science Centre
  • Ottawa Heart Institute
  • IUCPQ Chirurgie Cardiaque

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

AVR Low Risk without warfarin

AVR low risk with standard warfarin

AVR High risk with lower warfarin

AVR High Risk with standard warfarin

MVR with lower warfarin

MVR with standard warfarin

Arm Description

AVR Low Risk without warfarin

AVR low risk with standard warfarin

AVR High risk with lower warfarin

AVR High Risk with standard warfarin

MVR with lower warfarin

MVR with standard warfarin

Outcomes

Primary Outcome Measures

Thromboembolism
Rate of thromboembolism evaluated every 100 patient-years
Valve Thrombosis
Rate of thrombosis evaluated every 100 patient-years
Bleeding Events
Rate of major and minor bleeding events evaluated every 100 patient-years

Secondary Outcome Measures

Valve-Related Events
Rates of other valve-related events (e.g. prosthetic valve dysfunction, hemolysis, hemolytic anemia, endocarditis) every 100 patient-years
New York Heart Association (NYHA) classification
Functional classification at each follow-up
Valve Hemodynamics
Echocardiograpic measures of valve hemodynamics at 1, 3 and 5 years

Full Information

First Posted
February 10, 2006
Last Updated
September 13, 2022
Sponsor
On-X Life Technologies, Inc.
Collaborators
Clinipace Worldwide, Acelis Connected Health, WCG IRB, Avania
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1. Study Identification

Unique Protocol Identification Number
NCT00291525
Brief Title
Randomized On-X Anticoagulation Trial
Acronym
PROACT
Official Title
Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 6, 2006 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
On-X Life Technologies, Inc.
Collaborators
Clinipace Worldwide, Acelis Connected Health, WCG IRB, Avania

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Various patient groups with the On-X Valve can be maintained safely on lower doses of blood thinner(Coumadin®) or on antiplatelet drugs (aspirin/Plavix®) only rather than the standard dose of Coumadin and aspirin presently recommended by ACC/AHA or ACCP professional societies.
Detailed Description
This is a longitudinal, randomized (randomization to occur at the 3-month follow-up) study comparing the On-X valve on low dose anticoagulation (test group) to concomitant control groups of On-X valves receiving standard Coumadin/aspirin therapy, and also to FDA objective performance criteria (OPC) for heart valve replacement. It is a multicenter study consisting of up to 50 centers in the United States, Canada, and Italy enrolling and randomizing no more than 1200 patients (200 in each of 6 groups). There are three test arms of the study: low risk aortic valve replacement, high risk aortic valve replacement, and mitral valve replacement. Each arm has an equivalent control. Test therapies are: low risk aortic valve replacement - aspirin/Plavix, high risk aortic valve replacement - Coumadin at INR of 1.5 to 2.0 plus aspirin, and mitral valve replacement - Coumadin at an INR of 2.0 to 2.5 plus aspirin. Follow-up will run for up to 8 years in each patient. Each arm is independent and the low risk aortic and high risk aortic arms are completed. The low risk aortic arm was closed early resulting in a reduction of the estimated total enrollment with randomization to 1000. The high risk arm is completed with FDA review and this arm had 375 randomized enrollees. The mitral arm continues to enroll with a planned randomized enrollment of 400.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Valve Disease
Keywords
valve, prosthesis, antithrombotics, randomized

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AVR Low Risk without warfarin
Arm Type
Experimental
Arm Description
AVR Low Risk without warfarin
Arm Title
AVR low risk with standard warfarin
Arm Type
Active Comparator
Arm Description
AVR low risk with standard warfarin
Arm Title
AVR High risk with lower warfarin
Arm Type
Experimental
Arm Description
AVR High risk with lower warfarin
Arm Title
AVR High Risk with standard warfarin
Arm Type
Active Comparator
Arm Description
AVR High Risk with standard warfarin
Arm Title
MVR with lower warfarin
Arm Type
Experimental
Arm Description
MVR with lower warfarin
Arm Title
MVR with standard warfarin
Arm Type
Active Comparator
Arm Description
MVR with standard warfarin
Intervention Type
Device
Intervention Name(s)
On-X valve using reduced anticoagulation
Other Intervention Name(s)
On-X Prosthetic Heart Valve
Intervention Description
Valve replacement with antiplatelet agents or lowered warfarin
Intervention Type
Device
Intervention Name(s)
On-X Valve with Standard warfarin Therapy
Other Intervention Name(s)
On-X Prosthetic Heart Valve
Intervention Description
Valve replacement with standard dosage warfarin
Primary Outcome Measure Information:
Title
Thromboembolism
Description
Rate of thromboembolism evaluated every 100 patient-years
Time Frame
8 years
Title
Valve Thrombosis
Description
Rate of thrombosis evaluated every 100 patient-years
Time Frame
8 years
Title
Bleeding Events
Description
Rate of major and minor bleeding events evaluated every 100 patient-years
Time Frame
8 years
Secondary Outcome Measure Information:
Title
Valve-Related Events
Description
Rates of other valve-related events (e.g. prosthetic valve dysfunction, hemolysis, hemolytic anemia, endocarditis) every 100 patient-years
Time Frame
8 years
Title
New York Heart Association (NYHA) classification
Description
Functional classification at each follow-up
Time Frame
8 years
Title
Valve Hemodynamics
Description
Echocardiograpic measures of valve hemodynamics at 1, 3 and 5 years
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients requiring isolated aortic valve replacement (AVR), or isolated mitral valve replacement (MVR). AVR patients receiving low dose or antiplatelet only anticoagulation will be divided into groups at low risk and high risk for thromboembolism with all patients being in the low risk group except for patients with the following conditions which place a patient in the high risk group: Chronic atrial fibrillation Left ventricular ejection fraction < 30 % Enlarged left atrium >50mm diameter Spontaneous echo contrasts in the left atrium Vascular pathology Neurological events Hypercoagulability Left or right ventricular aneurysm Lack of platelet response to aspirin or clopidogrel Women receiving estrogen replacement therapy Concomitant cardiac surgery is allowed Adult patients Exclusion Criteria: Right side valve replacement Double (aortic plus mitral) valve replacement Patients with active endocarditis at the time of implant Previous confirmed or suspected thromboembolic event or thrombophlebitis Other terminal illness Patients who are in an emergency state Inability to return for required follow-ups Patients with an On-X valve implanted within the study and subsequently explanted Patients who are known to be pregnant, plan to become pregnant or are lactating Patients with acquired immunodeficiency syndrome or know to be HIV positive Patients who are prison inmates or known drug or alcohol abusers Patients unable to give adequate informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Puskas, MD
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Study Director
Facility Information:
Facility Name
Tucson Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85718
Country
United States
Facility Name
Southern Arizona VA Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85723
Country
United States
Facility Name
Loma Linda University
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Christiana Health Care Services
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Medstar Heart & Vascular Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Shands Hospital - University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Cardiac Surgical Associates
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Facility Name
South Florida Heart & Lung
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Florida Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30365
Country
United States
Facility Name
St. Francis Heart Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Cotton-O'Neil Clinical Research Center
City
Topeka
State/Province
Kansas
ZIP/Postal Code
66604
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
St. Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48197
Country
United States
Facility Name
Mid America Heart institute
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Barnes Jewish Hospital - Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New Mexico Heart Institute
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
St. Luke's Roosevelt
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Montefiore Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
WakeMed
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Facility Name
Duke University Medical Center
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Novant Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27104
Country
United States
Facility Name
University Hospital - Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Oklahoma/VA Oklahoma City
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Providence Heart & Vascular Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97220
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Baylor Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75226
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Heart Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77225
Country
United States
Facility Name
Texas Cardiac Center
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Baylor Scott & White - Plano
City
Plano
State/Province
Texas
ZIP/Postal Code
78093
Country
United States
Facility Name
Mary Washington Hospital
City
Fredericksburg
State/Province
Virginia
ZIP/Postal Code
22401
Country
United States
Facility Name
Sentara Norfolk General Hospital
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
MultiCare Health System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98415
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
St. Luke's Aurora Health Care
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
76G 2B7
Country
Canada
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
London Health Science Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
IUCPQ Chirurgie Cardiaque
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30286937
Citation
Puskas JD; PROACT Investigators. Reply: Low-Thrombogenicity Mechanical Heart Valves: Which Antithrombotic Strategy? J Am Coll Cardiol. 2018 Oct 9;72(15):1879-1880. doi: 10.1016/j.jacc.2018.07.063. No abstract available.
Results Reference
background
PubMed Identifier
24512654
Citation
Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12.
Results Reference
result
PubMed Identifier
29504958
Citation
Yanagawa B, Levitsky S, Puskas JD; PROACT Investigators. Reduced anticoagulation is safe in high-risk patients with the On-X mechanical aortic valve. Curr Opin Cardiol. 2015 Mar;30(2):140-145. doi: 10.1097/HCO.0000000000000149.
Results Reference
result
PubMed Identifier
29903344
Citation
Puskas JD, Gerdisch M, Nichols D, Fermin L, Rhenman B, Kapoor D, Copeland J, Quinn R, Hughes GC, Azar H, McGrath M, Wait M, Kong B, Martin T, Douville EC, Meyer S, Ye J, Jamieson WRE, Landvater L, Hagberg R, Trotter T, Armitage J, Askew J, Accola K, Levy P, Duncan D, Yanagawa B, Ely J, Graeve A; PROACT Investigators. Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement. J Am Coll Cardiol. 2018 Jun 19;71(24):2717-2726. doi: 10.1016/j.jacc.2018.03.535.
Results Reference
result
PubMed Identifier
35101419
Citation
Chu MWA, Ruel M, Graeve A, Gerdisch MW, Damiano RJ Jr, Smith RL 2nd, Keeling WB, Wait MA, Hagberg RC, Quinn RD, Sethi GK, Floridia R, Barreiro CJ, Pruitt AL, Accola KD, Dagenais F, Markowitz AH, Ye J, Sekela ME, Tsuda RY, Duncan DA, Swistel DG, Harville LE 3rd, DeRose JJ, Lehr EJ, Puskas JD; PROACT Mitral Investigators. WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial. Ann Thorac Surg. 2022 Jan 28:S0003-4975(22)00138-2. doi: 10.1016/j.athoracsur.2022.01.015. Online ahead of print.
Results Reference
derived

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Randomized On-X Anticoagulation Trial

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